Feature Articles

Making Improvements to Standard of Care for HCV

Small Molecule Combination Therapies Are Being Investigated to Increase Response Rates

Nucleoside Inhibitors

“We’ve been working on nucleoside inhibitors of NS5B,” said Michael J. Sofia, Ph.D., vp, chemistry at Pharmasset. Compound R7128 is in clinical development as part of their collaboration with Roche. R7128 has gone through several clinical studies with genotypes 1, 2, and 3; patients with all genotypes have responded well to therapy. “We were the first company to demonstrate clinical efficacy in genotype 2 and 3 patients with a direct acting antiviral agent. At a 1,000 mg BID dose in combination with interferon and ribavirin we saw a rapid virological response where 90 percent of the patients went to undetectable.”

In addition, Dr. Sofia will discuss PSI-7851, a nucleoside prodrug that specifically targets treatment to the liver. “We anticipate filing an IND imminently, certainly within 1Q of 2009.”

“One of the key takeaways is that nucleosides are effective and safe agents for the treatment of HCV,” Dr. Sofia says. “They are unique among all current experimental treatments in that they show a high barrier to resistance and broad genotype coverage. We believe that they will become an integral part of any treatment regimen and certainly will be a mainstay of future therapies in the field. This is one of several strategies we have in place, as we have multiple programs in nucleosides. Our strategy is to develop proprietary combinations for treatment of HCV.”

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